Pharmaceutically acceptable excipients can be classified according to their hydrophilicy/hydrophobicity index and the transfer (Gibbs) free energy associated with the transition of excipients from one phase to another, such as from water to vapor (i.e. delta Gwater-vapor). Kyte and Doolittle described the hydrophobicity index as a scale in which the tendency of the molecule to segregate into either the polar or non-polar phases is rank ordered (Kyte and Doolittle (1982) J. Mol. Biol. 157, 105-132). They have reported on the hydrophobicity of the 20 amino acids based on their relative abundance in various structural segments of proteins (hydropathy index). Based on these studies, the amino acids were arranged in the order of increasing hydrophobicity, e.g. higher frequency with which the amino acids are found in the core of the proteins. In a similar manner, other molecules such as peptides, proteins, and polymers can be classified according to the hydropathy index.
The current invention uses the hydropathy index or transfer (Gibbs) free energy as a guide in selecting the molecules that can be added to a solution to engineer the formation of particles with the desired characteristics (i.e. dispersibility, fine particle fraction, etc.).